Myasthenia gravis (MG) is an autoimmune disease associated with circulating antibodies, either against the nicotinic acetylcholine receptor (anti-AChR; ~80% of patients with generalised MG) or muscle-specific tyrosine kinase (anti-MuSK, 10% of patients),1 that induce a dysfunction of neuromuscular transmission owing to loss of functional receptors. Less commonly, MG remains confined to the ocular muscles. Only about 50% of such patients have antibodies detectable by standard assay (almost invariably anti-AChR) and most respond well to moderate doses of steroids without the need for more aggressive immunosuppression. In addition to anticholinesterase drugs, most patients with generalised MG require long-term treatment with steroids and immunosuppressive drugs, of which the most commonly used include azathioprine, mycophenolate mofetil and ciclosporin.2–5 Between 5 and 10% of patients remain refractory to such treatment.2,6 Other immunosuppressive drugs may then be considered, including cyclophosphamide,7 tacrolimus8 and etanercept,9 whose efficiency has not been assessed on the basis of double-blind clinical trials. Intravenous immunoglobulins (IVIg)10 and plasma exchange11 are used for acute exacerbations while waiting for other treatments to become effective, but have no sustained beneficial effect. Newer effective molecules with a good safety profile are undoubtedly needed.
Rituximab (RTX), a chimaeric monoclonal antibody specific for human CD20 that targets B lymphocytes, was first developed (and licensed) for the treatment of B-cell lymphoma12,13 and is used at a dose of 375mg/m2/body surface area once weekly for four weeks. It was noted that in patients with lymphoma treated with RTX and concomitantly suffering from autoimmune diseases (rheumatoid arthritis [RA]14 or MG15) the autoimmune diseases were ameliorated. Subsequent to these early reports, RTX has been used in many autoimmune diseases where B cells seem to play a role, not only in RA. These pivotal studies16,17 led to the molecule being licensed in cases of RA resistant to antitumour necrosis factor (anti-TNF) first-line therapy (RTX 1g on days one and 15), and also being used (off-label) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis,18,19 multiple sclerosis,20,21 systemic lupus erythematosus (SLE),22 immune thrombocytopenic purpura (ITP)23 and pemphigus.24